We propose to use methods recently developed in this laboratory to generate monoclonal human-human hybridoma antibodies against the cell membrane antigens which define the phenotypes of different types of human neoplasms, with particular emphasis on the lymphomas and leukemias. In vitro assays will be used to select antibodies with high binding affinities and/or cytotoxicity for later use in clinical diagnosis and treatment of the corresponding neoplasms. After checking for monoclonality, sterility, and freedom from pyrogens, these antibodies will be tested over an increasing dose range in Phase I trials in patients with advanced neoplastic disease to establish acceptable dose levels. They will also be labeled with 125I or other suitable radionuclides and injected into Phase I patients to ascertain whether selective uptake can be reliably detected in primary neoplasms, regional lymph node metastases, and distant metastatic sites. These antibodies will be used in direct or indirect immunofluorescence and immunoperoxidase studies to assess their usefulness in the differential diagnosis of various types of lymphomas and in selected other types of neoplasms. If such Phase I studies yield encouraging results, randomized clinical trials will be performed to evaluate the efficacy of cytotoxic or radiolabeled monoclonal human antibodies in the adjuvant treatment of micrometastases in patients with lymphomas and leukemias, and subsequently in patients with other types of neoplastic disease, in whom complete remissions have been induced by conventional treatment. Preliminary consideration will also be given to molecular cloning of cDNA prepared from the mRNA of hybridomas producing selected, high-priority antibodies.